Membrane fusion must usually accompany biological processes such as secretion, hormone and enzyme release, intracellular transport and cell growth. The question of reorganization that must accompany fusion has been an important but intractable problem in membrane biology. Our results on membrane fusion during mucocyst secretion in Tetrahymena pyriformis have opened up an entirely new dimension in the study of membranes and led to our proposed hypothesis of membrane fusion. We have demonstrated specific interior membrane markers -rosettes- within the plasma membrane and corresponding ones -annulus- within the membrane of the secretory vesicle. These are formed via membrane rearrangement prior to fusion and accompanying discharge. The secretory vesicle migrates towards the site within the plasma membrane and only when it comes within a critical distance of the rosette does the rearrangement of its membrane takes place. Using isolated preparations (Cell fractionation) of mucocysts and membranes (pellicle) from Tetrahymena as our model, we shall try to elucidate the conditions that lead to membrane rearrangement of vesicular and plasma membranes, and attempt to analyze the role and biochemical characteristics of these specific membrane markers, utilyzing both conventional electron microscopy and the freeze-fracture, freeze-etch technique. We shall also attempt to verify specific aspects of our hypothesis for mammalian secretory systems such as the salivary gland, the adrenal medulla and certain synapses. We shall use high voltage electron microscopy to increase the probability of visualizing membrane markers in embedded material.